'''Plasmodium Falciparum Triosephosphate isomerase (PfTIM) compled to substrate analog glycerol-3-phosphate (G3P).'''
===Plasmodium Falciparum Triosephosphate isomerase (PfTIM) compled to substrate analog glycerol-3-phosphate (G3P).===
==Overview==
<!--
The glycolytic enzymes of Plasmodium falciparum (Pf) are attractive drug targets as the parasites lack a functional tricarboxylic cycle and hence depend heavily on glycolysis for their energy requirements. Structural comparisons between Pf triosephosphate isomerase (PfTIM) and its human homologue have highlighted the important differences between the host and parasite enzymes [Velanker et al. (1997), Structure, 5, 751-761]. Structures of various PfTIM-ligand complexes have been determined in order to gain further insight into the mode of inhibitor binding to the parasite enzyme. Structures of two PfTIM-substrate analogue complexes, those of 3-phosphoglycerate (3PG) and glycerol-3-phosphate (G3P), have been determined and refined at 2.4 A resolution. Both complexes crystallized in the monoclinic space group P2(1), with a molecular dimer in the asymmetric unit. The novel aspect of these structures is the adoption of the 'loop-open' conformation, with the catalytic loop (loop 6, residues 166-176) positioned away from the active site; this loop is known to move by about 7 A towards the active site upon inhibitor binding in other TIMs. The loop-open form in the PfTIM complexes appears to be a consequence of the S96F mutation, which is specific to the enzymes from malarial parasites. Structural comparison with the corresponding complexes of Trypanosoma brucei TIM (TrypTIM) shows that extensive steric clashes may be anticipated between Phe96 and Ile172 in the 'closed' conformation of the catalytic loop, preventing loop closure in PfTIM. Ser73 in PfTIM (Ala in all other known TIMs) appears to provide an anchoring water-mediated hydrogen bond to the ligand, compensating for the loss of a stabilizing hydrogen bond from Gly171 NH in the closed-loop liganded TIM structures.
The line below this paragraph, {{ABSTRACT_PUBMED_12454456}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 12454456 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_12454456}}
==About this Structure==
==About this Structure==
Line 30:
Line 34:
[[Category: Enzyme-inhibitor complex]]
[[Category: Enzyme-inhibitor complex]]
[[Category: Tim barrle]]
[[Category: Tim barrle]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:44:11 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:23:31 2008''
Revision as of 23:23, 2 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
Structures of Plasmodium falciparum triosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state., Parthasarathy S, Balaram H, Balaram P, Murthy MR, Acta Crystallogr D Biol Crystallogr. 2002 Dec;58(Pt 12):1992-2000. Epub, 2002 Nov 23. PMID:12454456
